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Multiple signaling pathways that promote tumor cell metastasis are differentially activated in low/non-metastatic and metastatic tumor cells, resulting in the differential expression of metastasis-related genes. The underlying mechanism may involve the alterations of the intrinsic negative regulation in tumor cells. Here we report that the differential expression of interleukin-37b (IL-37b) in tumor cells alters the intrinsic negative regulation of signaling pathways, resulting in the difference of metastatic capacity. IL-37b could bind Smad3 and suppress Smad pathway by interfering with the formation and nuclear translocation of Smad2/3/4 complex. In turn, Smad3 could function as a co-regulator, enabling IL-37b to suppress multiple non-Smad pathways. IL-37b-Smad3 translocated into nucleus to upregulate the expression of non-receptor protein tyrosine phosphatases (PTPNs), thus promoting dephosphorylation to suppress the activation of tyrosine phosphorylation-dependent signaling pathways such as ERK, p38 MAPK, JNK, PI3K, NF-κB, and STAT3 pathways. Intriguingly, 13 of 17 PTPNs, most of which are metastasis suppressors, were downregulated in metastatic tumor cells because of the low expression of IL-37b. The marked decrease of intracellular IL-37b attenuated the intrinsic negative regulation in tumor cells, resulting in the enhanced activation of multiple signaling pathways and the increased capacity of invasiveness and metastatic colonization. Consistently, low expression of IL-37b in tumors was significantly associated with poor prognosis of cancer patients. Taken together, these findings reveal that intracellular IL-37b is a critical factor in the negative regulation of multiple signaling pathways that modulate the expression of metastasis-related genes, and suggest that IL-37b expression in tumor cells can potentially be a histopathological prognostic parameter for cancer patients and a therapeutic target for preventing tumor metastasis.

This study was conducted with an ovine intrauterine growth restriction (IUGR) model to test the hypothesis that dietary N-carbamylglutamate (NCG) and rumen-protected L-Arg (RP-Arg) supplementation are effective in ameliorating fetal growth restriction in undernourished ewes. Beginning on d 35 of gestation, ewes were fed a diet providing 100% of NRC-recommended nutrient requirements, 50% of NRC recommendations (50% NRC), 50% of NRC recommendations supplemented with 20 g/d RP-Arg (providing 10 g/d of Arg), and 50% of NRC recommendations supplemented with 5 g/d NCG product (providing 2.5 g/d of NCG). On d 110, maternal, fetal, and placental tissues and fluids were collected and weighed. Ewe weights were lower (P< 0.05) in nutrient-restricted ewes compared with adequately fed ewes. Maternal RP-Arg or NCG supplementation did not alter (P= 0.26) maternal BW in nutrient-restricted ewes. Weights of most fetal organs were increased (P< 0.05) in RP-Arg–treated and NCG-treated underfed ewes compared with 50% NRC-fed ewes. Supplementation of RP-Arg or NCG reduced (P< 0.05) concentrations of β-hydroxybutyrate, triglycerides, and ammonia in serum of underfed ewes but had no effect on concentrations of lactate and GH. Maternal RP-Arg or NCG supplementation markedly improved (P< 0.05) concentrations of AA (particularly arginine-family AA and branched-chain AA) and polyamines in maternal and fetal plasma and in fetal allantoic and amniotic fluids within nutrient-restricted ewes. These novel results indicate that dietary NCG and RP-Arg supplementation to underfed ewes ameliorated fetal growth restriction, at least in part, by increasing the availability of AA in the conceptus and provide support for its clinical use to ameliorate IUGR in humans and sheep industry production.

Ovarian steroid hormones regulate follicular growth and atresia. This study aims to determine whether key ovarian sterol-regulatory genes are differentially expressed in Hu sheep under different short-term nutritional regimens. Estrus was synchronized using intravaginal progestagen sponges. The ewes were assigned randomly to 3 groups. On d 6 to 12 of their estrous cycle, the control (CON) group received a maintenance diet (1.0 × M), the supplemented (SUP) group received 1.5 × M, and the restricted (R) group received 0.5 × M. On d 7 to 12, blood samples were taken. The sheep were slaughtered at the end of the treatment, and their organs and ovaries were collected. The plasma concentrations of urea (P< 0.01), total cholesterol (P< 0.01), low-density lipoprotein cholesterol (P< 0.01), NEFA (P< 0.01), FSH (P< 0.05), and estradiol (P< 0.05) increased with decreasing dietary intake, whereas plasma triglyceride (P< 0.01) and triiodothyronine (T3) concentrations decreased (P< 0.05). The ewes in the R group had higher spleen weight and percentage of spleen to BW and lower liver and small intestine weights and percentage of liver/stomach to BW than the SUP group ewes (P< 0.05). Nutritional restriction decreased the cytochrome p450 (CYP17A1) and estrogen receptor 1 (ESR1) mRNA expression (P< 0.05) and increased the cytochrome p450 aromatase (CYP19A1) mRNA expression (P< 0.05) in follicles > 2.5 mm. Follicle size affected the mRNA expression of very low density lipoprotein receptor (VLDLR), estrogen receptor 2 (ESR2), FSH receptor (FSHR), CYP17A1,and CYP19A1(P< 0.05). In conclusion, we suggest that a potential mechanism by which short-term negative energy balance inhibits follicular growth may involve responses to disrupted reproductive hormone concentrations and influenced the intrafollicular expression of CYP17A1, CYP19A1,and ESR1. This result may be due to increased plasma urea and lipid concentrations.

A simulation model is developed to study the dynamic characteristics of intermittent turning operations. Factors such as chip load, free-vibration of the toolpost structure, and nonhomogeneous hardness distribution in the material being cut are incorporated in the model. The principle of superposition is used in the formulation of the simulation algorithm. The impact between the cutting tool and the workpiece at the start of every cutting period during machining is treated as an initial value problem. The simulation model provides a quantitative evaluation of the tool vibratory motion during the intermittent turning process. Study of the cutting dynamics based on the simulation results not only confirms the experimental findings, but also indicates that increasing the static stiffness of the toolpost structure is an effective approach to control the tool vibratory motion. The determination of probability of tool breakage under various spindle speed settings is presented as an example to demonstrate the practical applications of the simulation model developed in this work.

This paper presents a methodology which employs computer simulation to dynamically generate the topography of a surface machined during an intermittent turning process. The methodology is based on a mathematical model that characterizes the intermittent turning process as an alternating sequence of forced and free vibratory motion. The simulation of machining workpieces, with discontinuous geometries of arbitrary shape, is facilitated by representing the workpiece surface as a two-dimensional grid, with an index for each cell in the grid accounting for the feature boundaries. The tool vibratory motion is integrated with the tool geometric motion to form a basis for the construction of surface texture produced during machining. The simulation model not only provides for a qualitative evaluation of the surface accuracy through a graphic visualization of the surface topography, but also provides a quantitative estimate of the roughness quality of the machined surface.

Cervical root nerve transfer from the contralateral side has been used for the treatment of brachial plexus root avulsion in 49 patients. Resection of C7 root from the healthy side has produced no long-term symptoms or signs. Nine patients with ten recipient nerves have been followed up for more than two years and seven have obtained a functional recovery. This operation offers a new approach for the treatment of brachial plexus root avulsion.

A simulation model is developed to study the dynamic characteristics of intermittent turning operations. Factors such as chip load, free-vibration of the toolpost structure, and nonhomogeneous hardness distribution in the material being cut are incorporated in the model. The principle of superposition is used in the formulation of the simulation algorithm. The impact between the cutting tool and the workpiece at the start of every cutting period during machining is treated as an initial value problem. The simulation model provides a quantitative evaluation of the tool vibratory motion during the intermittent turning process. Study of the cutting dynamics based on the simulation results not only confirms the experimental findings, but also indicates that increasing the static stiffness of the toolpost structure is an effective approach to control the tool vibratory motion. The determination of probability of tool breakage under various spindle speed settings is presented as an example to demonstrate the practical applications of the simulation model developed in this work.

This paper presents a methodology which employs computer simulation to dynamically generate the topography of a surface machined during an intermittent turning process. The methodology is based on a mathematical model that characterizes the intermittent turning process as an alternating sequence of forced and free vibratory motion. The simulation of machining workpieces, with discontinuous geometries of arbitrary shape, is facilitated by representing the workpiece surface as a two-dimensional grid, with an index for each cell in the grid accounting for the feature boundaries. The tool vibratory motion is integrated with the tool geometric motion to form a basis for the construction of surface texture produced during machining. The simulation model not only provides for a qualitative evaluation of the surface accuracy through a graphic visualization of the surface topography, but also provides a quantitative estimate of the roughness quality of the machined surface.

With increasing emphasis on the adaptive control for the purpose of quality and productivity improvement, it becomes necessary to develop models which can correlate the surface finish parameters with the machining conditions as well as work-piece material characteristics. This paper presents a study that leads to the development of a model for the dynamic generation of three-dimensional texture of machined surfaces. In Part 1, the mathematical formulation of the random excitation system which is responsible for the random portion of a surface profile is developed. It is assumed that the random excitation system originates from the nonhomogeneous distribution of microhardness of workpiece material. Machining tests are also performed to verify the validity of such a model development. In Part 2, a procedure for the construction of three-dimensional topography will be developed and the relationship between the machining conditions and the surface finish parameters will be established.

In Part 1 of these two-part papers, a normal distribution model has been formulated to describe the random excitation system present during machining. Part 2 presents a methodology to dynamically generate the surface topography under the random excitation environment through computer simulation. The proposed methodology uses the tool vibratory motion along with the tool geometrical motion to construct the topography of a machined surface. Both experimental and simulation results confirm that when a small feed is used, the influence of the spiral trajectory of tool geometrical motion on the surface generation decays dramatically and the random excitation system, on the opposite, is strengthened playing a significant role in surface texture generation.

A system of model formulated in the state variable space is proposed to describe the dynamic characteristics of the boring machining system. Particular attention is paid to the effect of the tangential vibration on the system performance. Modal analysis in the eigenvector space is employed to derive the analytical form of the system response. Experiments are carried out under spiral cutting conditions and the critical cutting stiffness predicted by the proposed model is compared with corresponding measured values, showing good agreements.

This paper reported experience with application of the snuff-box cutaneous flap in 10 patients with skin contracture in the hands. The sites with skin contracture were the first web sight in six, dorsal wrist in two, and palmar wrist in two. The flap was harvested centred by the snuff-box region with a width of 3 to 5 cm and length of 10 to 14 cm. This flap was based on the perforating branches from the radial artery in the snuff-box area. The pedicle of the flap was 4.2 mm in length. Venous drainage was through two concomitant veins of the perforating branch and the cephalic vein. Clinical application of this flap produced good results in nine cases and partial necrosis in one due to venous congention. This local cutaneous flap of the hand is recommended as a rotational pedicle flap to cover skin defects in the first web or the wrist regions. However, the flap may have disadvantages, such as failure of adequate venous return due to flap rotation or the necessity for a skin graft in the donor area when the flap is large.

In five cases of total root avulsion injury of brachial plexus, the thenar branch of the median nerve and the deep branch of the ulnar nerve were sutured to the branches of the femoral nerve during the procedure of intercostal, phrenic, accessory nerve transfer to the nerve trunks. The suture of the distal median or ulnar nerve in the hand to the femoral nerve was to maintain intrinsic muscles and prevent their atropy before arrival of nerve regeneration from the proximal end. The suture of the nerves was protected by wrapping it by abdominal flaps. The median and the ulnar nerve branches were separated from the femoral nerve when the NAP or SEP became detectable (about 1.5 years after the initial surgery). Good function of intrinsic muscles of the hand was observed in these five cases during the course of follow-up of the initial surgery, but the nerve recovery was not good after resuture of the median and the ulnar nerves. It was suggested from this preliminary clinical observation that suture of the distal median and ulnar nerves with the other nerves is effective in preservation of intrinsic muscle function, but recovery of intrinsic muscle function by resuture of the median and the ulnar nerves is not good.